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Downregulation of IGF-IR expression by RNAi inhibits proliferation and enhances chemosensitization of human colon cancer cells

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Colon cancer is the second leading cause of cancer death worldwide. Elevated expression of insulin-like growth factor-I receptor (IGF-IR) is a frequent genetic abnormality seen in this malignancy. For a better understanding of its role in maintaining the malignant phenotype, we used RNA interference (RNAi) directed against IGF-IR in our study. The aim of this study was to examine the anti-proliferation and chemosensitization effects elicited by a decrease in the transcription and protein levels of IGF-IR by RNAi in SW480 colon cancer cells.

Methods

A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting IGF-IR to reduce its expression in SW480 cells. Western blot analysis was used to measure the protein level of IGF-IR. We assessed the effects of IGF-IR silencing on cancer cell growth by a cell growth curve. The effect of the 5-fluorouracil (5-FU)-induced cell death by knockdown of IGF-IR was also investigated by methyl thiazolyl tetrazolium assay.

Results

Transfection of siRNA targeting IGF-IR was shown to reduce IGF-IR messenger RNA levels by 95%. Western blotting detected a similar inhibition of IGF-IR protein levels in those cells. The cells transfected with PKD-short hairpin RNA-IGF-IR-V2 significantly decreased cell growth and rendered cells more sensitive to chemotherapy. The highest proliferation inhibitory and chemosensitization ratios were 53 ± 2% and 1.78, respectively.

Conclusion

This study indicates that downregulation of IGF-IR results in significant inhibition of tumor growth in vitro. It also provides a promising strategy to chemotherapy efficacy in human tumors and forming a basis for future in vivo trials.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, School of Medical Sciences, Tarbiat Modares University, P. O. Box: 14115-331, Tehran, Iran

    Kamal Yavari, Mohammad Taghikhani & Seyed A. Mesbah-Namin

  2. Nuclear Sciences and Technology Research Institute, Tehran, Iran

    Mohammad Ghannadi Maragheh & Mohammad Hossein Babaei

Authors
  1. Kamal Yavari
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  2. Mohammad Taghikhani
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  3. Mohammad Ghannadi Maragheh
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  4. Seyed A. Mesbah-Namin
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  5. Mohammad Hossein Babaei
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Correspondence to Mohammad Taghikhani.

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Yavari, K., Taghikhani, M., Ghannadi Maragheh, M. et al. Downregulation of IGF-IR expression by RNAi inhibits proliferation and enhances chemosensitization of human colon cancer cells. Int J Colorectal Dis 25, 9–16 (2010). https://doi.org/10.1007/s00384-009-0783-2

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  • DOI: https://doi.org/10.1007/s00384-009-0783-2

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